IP Library › Granted Patent US 12679838
Granted Patent B2
US 12679838 · App. 18/157,397 · Granted Jul 14, 2026

Aromatic compound and application thereof in antitumor drug

Inventors: Qiang Zhang (Shanghai, CN); Fengtian Du (Shanghai, CN); Haibo Wang (Shanghai, CN); Na Guo (Shanghai, CN); Tao Zhang (Shanghai, CN)
Assignee: Shanghai Zheye Biotechnology Co., Ltd.
C07D471/04
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Quick Facts
Patent No.
US 12679838
App. No.
18/157,397
Filed
Jan 20, 2023
Granted
Jul 14, 2026
Kind
B2
Art Unit
1624
USPC
546/113
Abstract

An aromatic compound protein inhibitor, a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, a method related to the preparation and use of the compound, a pharmaceutical composition comprising the compound, and a relevant cancer treatment method. The aromatic compound has selective and significant inhibitory activity on a protein, and has a wide application prospect in the field of tumor treatment.

Claims (76)

1 . A compound represented by formula (II), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof,

wherein, X is a nitrogen atom or CR 4 , and Y is a nitrogen atom or CR 5 ;

U is a nitrogen atom or CR U , wherein R U is hydrogen or deuterium;

R 1 , R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 3a , R 3b , R 3c , R 4 , R 5 , R 11 , R 12 , R 13 , and R 14 are each independently selected from hydrogen, deuterium, halogen, alkyl or deuterated alkyl;

R 15a is hydrogen or deuterium;

R 6a , R 6b , R 6c , R 6d , R 6e , R 6f , R 6g , and R 6h are each independently selected from hydrogen, deuterium, methyl or trideuteriomethyl;

R 7 is fluorine or chlorine; and

R 8 , R 9 , and R 10 are each independently selected from hydrogen, deuterium or fluorine;

wherein, the structural segment

is selected from the following structures:

wherein, the structural segment

is selected from the following structures:

wherein, the structural segment

is selected from the following structures:

 and

wherein, the structural segment

is selected from the following structures:

2 . The compound according to claim 1 , wherein the compound is represented by formula (III), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof,

wherein, X is a nitrogen atom or CR 4 , and Y is a nitrogen atom or CR 5 ;

R 1 , R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 3a , R 3b , R 3c , R 4 , R 5 , R 11 , R 12 , R 13 , and R 14 are each independently selected from hydrogen, deuterium, halogen, alkyl or deuterated alkyl;

R 15a is hydrogen or deuterium;

R 6a , R 6b , R 6c , and R 6d are each independently selected from hydrogen, deuterium, methyl or trideuteriomethyl;

R 7 is fluorine or chlorine; and

R 8 , R 9 , and R 10 are each independently selected from hydrogen, deuterium or fluorine;

wherein, the structural segment

is selected from the following structures:

wherein, the structural segment

is selected from the following structures:

wherein, the structural segment

is selected from the following structures:

 and

wherein, the structural segment

is selected from the following structures:

3 . The compound represented according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from:

4 . The compound according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from:

5 . The compound according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from:

6 . The compound according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from:

7 . The compound according to claim 1 , wherein the compound is represented by formula (IIIM), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof,

wherein, an axial chiral stereoconfiguration formed by connecting a nitrogen atom at the 1 position of the ring E with a carbon atom at the 1′ position of the ring F is optically pure; and

X is a nitrogen atom or CR 4 , and Y is a nitrogen atom or CR 5 ;

R 1 , R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 3a , R 3b , R 3c , R 4 , R 5 , R 11 , R 12 , R 13 , and R 14 are each independently selected from hydrogen, deuterium, alkyl or deuterated alkyl;

R 15a is hydrogen or deuterium;

R 6a , R 6b , R 6c , R 6d , R 6e , R 6f , R 6g , and R 6h are each independently selected from hydrogen, deuterium, methyl or trideuteriomethyl;

R 7 is fluorine or chlorine; and

R 8 , R 9 , and R 10 are each independently selected from hydrogen, deuterium or fluorine;

wherein, the structural segment

is selected from the following structures:

wherein, the structural segment

is selected from the following structures:

wherein, the structural segment

is selected from the following structures:

 and

wherein, the structural segment

is selected from the following structures:

8 . The compound according to claim 1 , wherein the compound is represented by formula (IIIM-1), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof,

wherein:

R 1 , R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 11 , R 12 , R 13 , and R 14 are each independently selected from hydrogen, deuterium, alkyl or deuterated alkyl;

R 15a is hydrogen or deuterium;

R 6a , R 6b , R 6c , R 6d , R 6e , R 6f , R 6g , and R 6h are each independently selected from hydrogen, deuterium, methyl or trideuteriomethyl;

R 7 is fluorine or chlorine;

R 8 , R 9 , and R 10 are each independently selected from hydrogen, deuterium or fluorine; and

R 17 is methyl, ethyl, deuterated methyl or deuterated ethyl;

wherein, the structural segment

is selected from the following structures:

wherein, the structural segment

is selected from the following structures:

 and

wherein, the structural segment

is selected from the following structures:

9 . The compound according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from:

10 . The compound according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from the following compounds with an axial chiral stereoconfiguration as R configuration:

11 . The compound according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from the following compounds with an axial chiral stereoconfiguration as R configuration:

12 . The compound according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from:

13 . The compound according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is axially chiral.

14 . A pharmaceutical composition, comprising an effective dose of the compound, or the stereoisomer, the tautomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier.

15 . A method for treating pancreatic cancer or lung cancer comprising administering a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof according to claim 1 , or a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, wherein the compound or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof is capable of being used alone or in combination with other therapeutic methods comprising immunotherapy.